Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of silymarin treatment in preventing biochemical and histological alterations in CCL4-induced liver cirrhosis in rats was studied. Four groups of rats were treated with: (1) CCL4; (2) mineral oil; (3) CCL4 + silymarin; and (4) silymarin. All animals were sacrificed 72 h after the end of treatments. The activities of alkaline phosphatase (alk. phosp.), gamma-glutamyl transpeptidase (GGTP), glutamic pyruvic transaminase (GPT) and glucose-6-phosphatase (G6Pase), and bilirubin content were determined in serum. Na+, K+-ATPase and Ca++-ATPase activities were measured in isolated plasma membranes. Lipoperoxidation, triglycerides (TG), and glycogen contents were also measured in liver homogenates. Liver cirrhosis was evidenced by significant increases in liver collagen, lipoperoxidation, serum activities of alk. phosp., GGTP, GPT, G6Pase, bilirubin content, and liver TG. Activities of ATPases determined in plasma membranes were significantly reduced, as was liver glycogen content. Silymarin cotreatment (50 mg/kg b.wt) completely prevented all the changes observed in CCL4-cirrhotic rats, except for liver collagen content which was reduced only 30% as compared to CCL4-cirrhotic rats. Silymarin protection can be attributed to the agent's antioxidant and membrane-stabilizing actions.
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PMID:Prevention of CCL4-induced liver cirrhosis by silymarin. 254 40

Microsomal Na+,K+-ATPase isolated from the renal cortex of rats with CCL4-induced cirrhosis (CIR) showed a higher specific activity than the enzyme obtained from control rats (COR). Kinetic studies showed a lower K0.5 for ATP (0.08 +/- 0.03 vs. 0.24 +/- 0.04 mM; p less than 0.05), a lower Na+ activation constant (9.6 +/- 1.5 vs. 19.0 +/- 1.7 mM; p less than 0.05), and a higher K+ activation constant (1.2 +/- 0.1 vs. 0.6 +/- 0.1 mM; p less than 0.05) for CIR. The optimal pH of the enzyme was 0.5 units higher in CIR than COR. The fluorescence of eosin-treated enzymes indicated a higher ratio of E1/E2 forms of Na+,K+-ATPase in CIR. The K+-activated p-nitrophenylphosphatase (pNPPase) activity of the enzyme was lower in CIR than COR rats (1.5 +/- 0.1 vs. 2.2 +/- 0.1 mU/mg; p less than 0.05). Dialysing (24 h) COR microsomes reproduced most of the changes observed in CIR enzymes (kinetics, optimal pH, and eosin fluorescence). Lyophilized dialysate of COR, but not of CIR microsomes, inhibits Na+,K+-ATPase activity. These results suggest that a dialysable inhibitor modifies the Na+,K+-ATPase activity in the kidney of COR which is almost absent in that of CIR. The absence of this factor may lead to the overall inability to excrete Na+ in the cirrhotic state.
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PMID:Absence of an endogenous regulator of Na+,K+-ATPase activity in the tissues of cirrhotic rats. 283 57

A decrease in sodium, potassium and anion (HCO3)-activated erythrocyte ATPases is noted in patients with acute viral hepatitides A and B, chronic persisting hepatitis, liver cirrhosis, chronic cholecystitis and in HBs-antigen carriers, the reduction of HCO8-ATPase being more noticeable. A degree of expression of the above changes depends on the severity of a pathological process in the liver. The most serious changes are noted in liver cirrhosis. In this disease calcium ATPase activity is also on a decrease. Erythrocyte ATPase activity is lowered in chronic cholecystitis to a lesser degree. In patients with chronic persisting hepatitis and liver cirrhosis erythrocyte ATPase activity slightly increases, however it remains significantly lowered as compared to the control level. The determination of erythrocyte ATPase activity can be used for assessment of the status of patients with acute and chronic liver diseases.
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PMID:[Comparative characteristics of adenosine triphosphatase activity in the erythrocytes of patients with acute and chronic liver diseases, chronic cholecystitis and in HBs antigen carriers]. 295 84

The potential promoting and/or complete carcinogenic activity of a methyl group-deficient (MD) diet lacking methionine, choline, vitamin B12, and folate on liver tumor induction in weanling male F344/NCr rats was examined. Each of 50 rats per group received one injection 20 mg diethylnitrosamine [(DENA) CAS: 55-18-5; N-nitrosodiethylamine]/kg body weight at 4 weeks of age, and then each was maintained on a methyl group-adequate (MA) diet for 52 weeks (groups 2 and 5) or on an MD diet for 15 weeks followed by the MA diet for 37 weeks (group 4). Controls received injections of saline and were maintained on the same two respective diet regimens (groups 1 and 3, respectively). Histologic results from sacrifices at 6, 10, 15, 22, 39, and 52 weeks revealed early development of foci of eosinophilic gamma-glutamyltransferase (GGT)-positive hepatocytes by week 6 in DENA-MD diet-treated rats, with subsequent development of a diffuse hyperplasia of hepatocytes, oval cell proliferation, cholangiofibrosis, nodular cirrhosis, and neoplastic nodule (NN) formation and, at 52 weeks, hepatocellular carcinomas (HCC) in 13 of 15 rats. Similar but significantly fewer lesions were observed at slightly later sacrifice times in the livers of saline-MD diet-treated rats, with development of NN in 5 of 12 rats and an HCC in 1 of 12 rats at 52 weeks. DENA-treated rats on MA diets developed relatively few GGT-positive foci, and none developed any neoplastic lesions. Except for basophilic foci, areas and foci of cellular alteration containing glycogen-rich hepatocytes frequently exhibited diminished uptake of injected iron and decreased glucose-6-phosphatase and ATPase contents focally or throughout. This study indicates that a relatively brief exposure of both untreated and DENA-treated weanling rats to a severely MD diet produces classical preneoplastic and neoplastic lesions in their livers.
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PMID:Profound postinitiation enhancement by short-term severe methionine, choline, vitamin B12, and folate deficiency of hepatocarcinogenesis in F344 rats given a single low-dose diethylnitrosamine injection. 659 43

Previous studies have demonstrated abnormalities of intracellular electrolyte content and sodium transport in leukocytes of patients with fulminant hepatic failure. The current study was undertaken to establish whether similar abnormalities were present in patients with encephalopathy from advanced cirrhosis. Results from 19 patients with advanced cirrhosis showed values for the leukocyte total sodium efflux-rate constant were significantly reduced in patients, 3.02 +/- 1 SEM 0.12 h-1, compared to control values, 3.80 +/- 0.06 h-1. This reduction was due primarily to a lowering of the ouabain-sensitive component of sodium efflux, a measure of Na,K-ATPase activity. In comparison, leukocytes from patients with fulminant hepatic failure show a greater inhibition of the ouabain-sensitive component of sodium efflux with a raised ouabain-insensitive efflux. Although cirrhosis has generally been associated with potassium depletion, the intracellular potassium content of the cirrhotic patients' leukocytes was normal. Since the leukocyte is considered to be a good cell model and because abnormalities of sodium transport have been shown in the leukocytes of these patients, it is likely that similar abnormalities of sodium transport are present in other organs, including the brain.
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PMID:Abnormalities in the leukocyte sodium pump in advanced cirrhosis. 726 13

Endogenous digitalis-like factor (EDLF), an inhibitor of membrane Na+/K(+)-ATPase, is discussed to be involved in the pathogenesis of cirrhogenic portal hypertension, ascites formation and development of functional hepatorenal failure. Therefore, we investigated the serum content of this mediator in patients with liver cirrhosis Child-Pugh stage A, B, and C (n = 27) by means of enzyme immunoassay with a specific digoxin antibody. Furthermore, a correlation analysis was performed in order to find out correlations between signs of cell injury, cholestasis, synthetic cell function, ascites formation, and hepatorenal failure. Our results demonstrate that EDLF is significantly elevated in Child C cirrhosis (0.61 +/- 0.15 ng/ml) in comparison to Child A cirrhosis (0.013 +/- 0.2 ng/ml) and is also higher than in Child B cirrhosis (0.23 +/- 0.25 ng/ml). In patients without ascites EDLF (0.056 +/- 0.19 ng/ml) differs significantly from that of patients with non-complicated ascites (0.156 +/- 0.176 ng/ml) and from that of patients with therapy refractory ascites (0.66 +/- 0.17 ng/ml) or hepatorenal failure (1.56 ng/ml). There are no correlations between EDLF and renal function. Significant correlations were demonstrated for cholestasis (serum bilirubin), synthesis function (serum protein, Quick's value, cholinesterase, fibrinogen, albumin), and the degree of portasystemic encephalopathy (number connection test). We conclude that EDLF may act as a mediator in the process of progressive portal hypertension and its complications due to cirrhosis. This process of progression is caused by the inhibition of Na+/K(+)-ATPase, vasoconstriction, and endothelin secretion.
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PMID:[Endogenous digitalis-like factor in liver cirrhosis and cholestasis]. 748 6

Wilson's disease is an autosomal recessive, inherited disorder of copper metabolism. In normal individuals, copper homeostasis is controlled by the balance between intestinal absorption of dietary copper and hepatic excretion of excess copper in bile. In Wilson's disease, hepatic copper is neither excreted in bile nor incorporated into ceruloplasmin and copper accumulates to toxic levels. The Wilson's disease gene (WND) encodes a putative copper-transporting protein that is expressed almost exclusively in the liver. The predicted structure of the protein product is that of a P-type ATPase with striking homology to bacterial copper transporters and the gene product of another inherited disorder of copper metabolism, Menkes' disease. A rat model of Wilson's disease has recently been identified. The Long-Evans Cinnamon (LEC) rat manifests elevated hepatic copper, defective incorporation of copper into ceruloplasmin, and reduced biliary excretion of copper. The rat homologue of the WND is abnormal in LEC rats. Clinical manifestations of Wilson's disease arise directly from copper-induced damage to hepatocytes (hepatic presentation) or indirectly after the release of copper from the liver with subsequent damage to the brain (neuropsychiatric presentation) and other organs. Genetic heterogeneity (different mutations in a single gene) may account for some of the variability in Wilsonian presentations. The diagnosis of Wilson's disease depends on the demonstration of disordered copper metabolism, manifested as elevated urinary and hepatic copper and low ceruloplasmin levels. However, none of the abnormal findings in Wilson's disease is pathognomonic. Genetic diagnosis, in the absence of family studies, is likely to be difficult since many different mutations result in the disease. Management of Wilson's disease involves decreasing excess levels of copper accumulated in the liver, brain, and other organs. Copper chelation therapy, to increase urinary excretion of copper, is the mainstay of treatment. In addition, oral zinc therapy may be useful at decreasing absorption of dietary copper and rendering tissue copper nontoxic, by increasing the formation of complexes with copper-binding proteins. Liver transplantation can be necessary for individuals with acute hepatic failure or complications of cirrhosis. Gene therapy may evolve in the future; however, medical management is effective in most patients.
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PMID:Wilson's disease: a new gene and an animal model for an old disease. 755 82

In this work we analyze the renal and systemic factors involved in the sodium retention in two conditions: in extracellular volume depletion and in edema forming states, particularly liver cirrhosis with ascitis. In this paper we accept that the volume loss of body fluids stimulates the "effective arterial blood volume" (VAE). This term results from a decrease in the arterial blood volume secondary to a fall in cardiac output or a peripheral arterial vasodilatation. The reduction in the VAE stimulates: the high pressure baroreceptors (carotid sinus and aortic arch); the intrarrenal mechanisms, such as the yuxtaglomerular apparatus and the renin angiotensin aldosterone system; the sympathetic adrenergic system; the non osmotic release of antidiuretic hormone; prostaglandins (PGE1, Tromboxane) and endothelin; and inhibits the atrial natriuretic peptide. We also describe the sodium transport mechanisms along the nephron during physiological conditions and after volume depletion, and in edema formation states, specially hepatic cirrhosis with ascitis. We speculate that the intrarenal mechanisms are more important and persistent than the systemic mechanisms. It is possible that the sodium retention of these states might be the result of direct stimuli of the tubular sodium transport mechanisms in the different segments of the nephron, mediated by the co and counter transports, ATPase activity or by the second messengers cyclic AMP and cyclic GMP. The clonation and structural characterization of the different sodium transports may help us to establish, more precisely, the intracellular tubular mechanisms responsible for the tendency of the body to retain sodium. The amount of information generated in the future may help us to demonstrate, with more precision, the mechanisms responsible for the sodium retention and excretion in normal and pathological conditions, particularly the edema forming states such as cardiac failure, nephrotic syndrome and hepatic cirrhosis with ascitis.
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PMID:[Renal and extra-renal mechanisms of sodium and water retention in cirrhosis with ascites]. 777 18

The aim of the present study was to evaluate the number of Langerhans' cells (LC) in immunosuppressed liver transplanted patients, compared to patients with liver cirrhosis and healthy volunteers. The detection of LC was performed in the epidermal sheet of each patient by using indirect immunoperoxidase and ATPase staining. A significant reduction in the number of LC was found in the liver transplanted patients as compared to patients with liver cirrhosis and healthy volunteers. This reduction may be related to prolonged treatment with corticosteroids and azathioprine.
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PMID:HLA-DR positive epidermal Langerhans' cells in liver cirrhosis and immunosuppressed liver transplanted patients. 791 35

In human and experimental CCl4-liver damage, S-adenosyl-l-methionine-synthetase and/or the intrahepatic content of S-adenosyl-l-methionine, are diminished and in human cirrhosis phospholipid methyltransferase is markedly reduced. Therefore the aim of this study was to investigate the effect of S-adenosyl-l-methionine administration on liver damage induced by 15-day bile duct ligation. Liver damage was analyzed by histological, ultrastructural and biochemical techniques. Biliary obstruction produced an increase in collagen content, dilation of the bile canaliculi and disorganization of mitochondria. These effects were not observed in the bile-duct-ligated group receiving S-adenosyl-l-methionine. Biochemical results showed that bile duct ligation increased serum bilirubins, and alkaline phosphatase and gamma-glutamyl transpeptidase activities. These effects were prevented significantly by S-adenosyl-l-methionine. On the other hand, glycogen content in the liver was depleted while lipid peroxidation was increased by biliary obstruction, S-adenosyl-l-methionine administration prevented these effects. In the bile-duct-ligated group, hepatocyte and erythrocyte plasma membrane Na+/K+ and Ca(2+)-ATPase were lower than in the control group (p < 0.05). Administration of S-adenosyl-l-methionine preserved ATPase activities. The exogenous S-adenosyl-l-methionine supply is probably responsible for restoring transmethylation lost in liver diseases.
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PMID:Protective effect of S-adenosyl-l-methionine on liver damage induced by biliary obstruction in rats: a histological, ultrastructural and biochemical approach. 796 28


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